1X7S

The X-ray crystallographic structure of the amyloidogenic variant TTR Tyr78Phe

1X7S の概要

• エントリーDOI: 10.2210/pdb1x7s/pdb
• 関連するPDBエントリー: 1X7T
• 分子名称: Transthyretin (2 entities in total)
• 機能のキーワード: transthyretin, familial amyoidotic polyneuropathy, amyloid, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27522.72

構造登録者

Neto-Silva, R.M.,Macedo-Ribeiro, S.,Pereira, P.J.B.,Saraiva, M.J.,Damas, A.M. (登録日: 2004-08-16, 公開日: 2005-03-22, 最終更新日: 2023-08-23)

主引用文献

Neto-Silva, R.M.,Macedo-Ribeiro, S.,Pereira, P.J.,Coll, M.,Saraiva, M.J.,Damas, A.M.
X-ray crystallographic studies of two transthyretin variants: further insights into amyloidogenesis.
Acta Crystallogr.,Sect.D, 61:333-339, 2005

PubMed Abstract: Transthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set of not yet fully characterized conformational changes, forms fibrillar aggregates that are the major protein component of amyloid deposits. More than 80 mutations associated with TTR amyloid deposition have been described in the literature. X-ray crystallography was used to elucidate the three-dimensional structure of two important TTR variants: TTR Y78F, an amyloidogenic protein, and TTR R104H, which is associated with a protective effect over the amyloidogenic V30M mutation. The structures of those two TTR variants have been determined in space group P2(1)2(1)2 to 1.55 and 1.60 angstroms resolution, respectively, using molecular-replacement techniques. Detailed analysis of the protein model for TTR Y78F indicates a destabilization of the contacts between the alpha-helix and AB loop and the body of the molecule, intimately related to the amyloidogenic nature; contrastingly, in the TTR R104H variant new contacts involving the N-terminal region and His104 are clearly antagonists of amyloid formation.

PubMed: 15735344
DOI: 10.1107/S0907444904034316

実験手法

X-RAY DIFFRACTION (1.55 Å)